Interferes with the formation of detailed memories by inhibiting the secretion of specific chemical transmitters in the amygdala
New research has identified the mechanism by which stress interferes with memory formation. The findings may help develop treatments for people with post-traumatic stress disorder and anxiety disorders. This is the content reported by the scientific journal “Nature” based on a paper by Canadian researchers published in “Cell” on the 15th (local time).
Stressed mice develop nerve cell bundles in their brains that interfere with memory formation, causing them to feel fear even in harmless situations. This explains why stressed people often feel threatened even in safe environments.
Scientists have long known that stress or trauma can cause fear even in harmless situations. For example, someone who is stressed after burning their finger on a hot pan may later avoid not only the hot pan, but also the kitchen or cooking itself. This type of generalized fear is common in people with post-traumatic stress disorder (PTSD) and generalized anxiety disorder.
Memories are made up of groups of nerve cells called engrams that are activated when memories are formed. The research team, led by Professor Sheena Josselin (physiology) at the University of Toronto School of Medicine in Canada, looked at whether stress interferes with engram formation and focused on an organ located in the limbic system called the amygdala, which is involved in stress and emotional responses.
This study went through elaborate three-stage experiments on mice. First, some adult mice were injected with the stress hormone corticosterone or confined in a small tube for 30 minutes to increase corticosterone levels and put them into a state of stress.
Then, stressed and non-stressed mice were placed in separate rooms, and a medium-pitched sound was played as a neutral event for 30 seconds. After a brief rest, the subjects were returned to the room, a high-pitched whistle was played for 30 seconds, and then their feet were shocked for 2 seconds to create a fear experience.
To test how the mice stored memories of these experiences, the researchers placed them in a new environment and played them two different pitches of sound and observed how they responded. While non-stressed mice froze primarily when they heard a high-pitched whistle, stressed mice responded to both sounds, suggesting that they were unable to distinguish between neutral and fearful events.
The researchers used a variety of techniques to visualize neural activity in rodents. As a result, they found that mice that were not stressed during the memory formation process formed small engrams in response to the whistle sound and foot shock, and that these engrams were reactivated only when exposed to the whistle sound. However, stressed mice formed larger engrams, which were reactivated when exposed to both sounds.
Additional experiments revealed a chain of events that generated larger engrams in the brains of stressed mice. Under normal conditions, certain nerve cells in the amygdala release a chemical transmitter called gamma-aminobutyric acid (GABA), which blocks neural activity. This creates small engrams in response to negative memories. Professor Jocelin explained, “This is similar to a velvet rope installed at the entrance of a nightclub,” and “It allows only specific nerve cells to enter the nightclub.”
However, when you are stressed, excitatory neurons pump the brain with neurotransmitters called endocannabinoids. Endocannabinoids bind to the glucocorticoid receptors of inhibitory neurons and prevent the release of GABA, causing engrams to become larger. In other words, when the velvet rope is removed, “many neurons are forced into the membership-only nightclub,” Professor Jocelin said.
Using two drugs, the researchers were able to reverse the effects of stress on memory formation. One of them is mifepristone, which was initially approved as an abortion medication. This drug blocked the production of glucocorticoid receptors or endocannabinoids, causing stressed rats to recall memories in the same way as non-stressed rats.
However, the researchers cautioned that the drug is unlikely to be useful to people because it has side effects that extend beyond the brain and is only effective when administered at the time memories are formed. The researchers are now investigating whether engrams can be altered after memories are formed, or whether there are other ways to mitigate the effects of stress on memory.
The paper can be found at the following link:
Source: kormedi.com